Heretofore, a method has generally been performed which comprises applying an adhesive skin patch containing a drug to the skin and allowing permeation of the drug from this adhesive skin patch to the skin, thereby administering the drug. On the other hand, administration methods using electrical energy, such as iontophoresis (Journal of Pharmaceutical Sciences, Vol. 76, p. 341, 1987) and electroporation (National Publication of International Patent Application No. 1991-502416; and Proc. Natl. Acad. Sci. USA, Vol. 90, p. 10504-10508, 1993), have been developed as methods for promoting drug absorption to the skin or mucous membrane. Iontophoresis and electroporation have both been expected to be utilized as methods for promoting transdermal or transmucosal drug absorption.
In connection with the promotion of drug absorption, National Publication of International Patent Application No. 2000-512529 (Patent Document 1) proposes an apparatus for mechanically piercing the skin before the release of transdermal pharmaceutical agents, thereby enhancing a transdermal flux thereof. This apparatus comprises a sheet having a plurality of openings, a plurality of microblades which are integrally formed therewith and extend downward therefrom, and means for anchoring the apparatus to the body surface. In this case, a dosage form in a pharmaceutical agent reservoir is, for example, an adhesive gel.
This kind of apparatus capable of retaining a drug in a dry form is, for example, a transdermal administration instrument for a protein or peptide drug described in Japanese Patent Publication No. 6-14980 (Patent Document 2), which comprises a skin needle. This instrument has a multilayer comprising an electrode leading to the outside, a polyelectrolyte tank, a hydrophilic polymer drug support, and a water-swellable polymer skin needle support, wherein a solvent inlet is formed in a central portion of the upper end of the polyelectrolyte tank. This solvent inlet is made of, for example, a rubber in the form of a V-shaped groove, through which an ionized solvent composition can be introduced to the inside of the polyelectrolyte tank by use of a syringe or the like. This instrument, when used, requires preparing an additional syringe or the like for introducing a solvent composition.
An apparatus which is capable of retaining a drug in a dry form and requires no syringe or the like is, for example, a transdermal delivery apparatus with a valve described in WO03/084595A1 (Patent Document 3). This apparatus comprises a reservoir capable of retaining, for example, distilled water, a valve for opening and closing this reservoir, a cavity capable of retaining a dry drug, and a plurality of micro skin penetrating members capable of penetrating the skin. This apparatus, when used, is disposed on the skin of a patient and pushed downward such that the micro skin penetrating members can penetrate the skin. Then, the valve is opened, and the reservoir is pressed, whereby the distilled water is supplied to the dry drug, thereby delivering the drug to the patient.
On the other hand, Japanese Patent Publication No. 5-84180 (Patent Document 4) discloses a novel plaster structure for iontophoresis. This plaster structure does not comprise such a skin needle. For example, a capsule filled with an electrolytic solution is provided in an upper portion of this plaster structure. This structure is constituted such that the structure, when applied to the skin, disrupts a thin film such as aluminum foil located between this capsule and a water-containing layer to infiltrate the electrolytic solution thereinto. When a water-soluble drug is used, the plaster structure may respond to a demand as a plaster structure comprising a capsule filled with an electrolytic solution, wherein drug-containing and water-containing layers are adjusted to be in a dry state.
Furthermore, coating techniques for microneedles have recently proceeded in various ways. For example, National Publication of International Patent Application No. 2004-504120 (Patent Document 5) discloses a drug delivery device having a skin piercing member comprising a solid biodegradable reservoir medium containing a drug. This reservoir medium is coated externally on the skin piercing member. As described therein, it is preferred that the reservoir medium should be sugars (lactose, raffinose, trehalose, or sucrose) dissolved by biodegradation to easily release the drug contained therein. Moreover, National Publication of International Patent Application No. 2004-528900 (Patent Document 6) discloses that a coating carrier for a microprojection array used in the transdermal administration of a vaccine or the like is selected from human albumin, polyglutamic acid, polyaspartic acid, polyhistidine, pentosan polysulfate, and polyamino acid. This coating carrier is also rapidly dissolved after skin penetration, thereby releasing a beneficial active substance. Furthermore, WO2005/016440A1 (Patent Document 7) discloses a coating carrier containing a polymer such as hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), dextran, polyvinyl alcohol, or polyethylene oxide. This carrier is flowable with a viscosity of 3 to 500 cps. Therefore, a needle tip is automatically coated with the carrier by designing the needle surface. Thus, as described therein, a coating procedure itself is unnecessary, and the duration of action can be rendered further longer. However, in this case, the coating carrier is forced to penetrate the skin and is therefore difficult to control. Thus, some doubt remains as to its practical use.    Patent Document 1: National Publication of International Patent Application No. 2000-512529    Patent Document 2: Japanese Patent Publication No. 6-14980    Patent Document 3: WO 2003/084595 A1    Patent Document 4: Japanese Patent Publication No. 5-84180    Patent Document 5: National Publication of International Patent Application No. 2004-504120    Patent Document 6: National Publication of International Patent Application No. 2004-528900    Patent Document 7: WO 2005/016440 A1